38. Yang J, Mani SA, Donaher JL, Ramaswamy S,
Itzykson RA, Come C, Savagner P,
Gitelman I, Richardson A, Weinberg RA
(2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939. https://doi.org/
10.1016/j.cell.2004.06.006
39. Skrypek N, Goossens S, De Smedt E,
Vandamme N, Berx G (2017) Epithelial-tomesenchymal transition: epigenetic reprogramming driving cellular plasticity. Trends
Genet 33(12):943–959. https://doi.org/10.
1016/j.tig.2017.08.004
40. Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG, Evers BM, Zhou BP (2012) G9a
interacts with snail and is critical for snailmediated E-cadherin repression in human
breast cancer. J Clin Invest 122
(4):1469–1486. https://doi.org/10.1172/
JCI57349
41. Lin T, Ponn A, Hu X, Law BK, Lu J (2010)
Requirement of the histone demethylase
LSD1 in Snai1-mediated transcriptional
repression during epithelial-mesenchymal
transition. Oncogene 29(35):4896–4904.
https://doi.org/10.1038/onc.2010.234
42. Peinado H, Ballestar E, Esteller M, Cano A
(2004) Snail mediates E-cadherin repression
by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol
Cell Biol 24(1):306–319. https://doi.org/
10.1128/mcb.24.1.306-319.2004
43. Herranz N, Pasini D, Diaz VM, Franci C,
Gutierrez A, Dave N, Escriva M,
Hernandez-Munoz I, Di Croce L, Helin K,
Garcia de Herreros A, Peiro S (2008) Polycomb complex 2 is required for E-cadherin
repression by the Snail1 transcription factor.
Mol Cell Biol 28(15):4772–4781. https://
doi.org/10.1128/MCB.00323-08
44. Tong ZT, Cai MY, Wang XG, Kong LL, Mai
SJ, Liu YH, Zhang HB, Liao YJ, Zheng F,
Zhu W, Liu TH, Bian XW, Guan XY, Lin
MC, Zeng MS, Zeng YX, Kung HF, Xie D
(2012) EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a
co-repressor complex with HDAC1/
HDAC2 and snail to inhibit E-cadherin.
Oncogene 31(5):583–594. https://doi.org/
10.1038/onc.2011.254
45. Aigner K, Dampier B, Descovich L,
Mikula M, Sultan A, Schreiber M,
Mikulits W, Brabletz T, Strand D, Obrist P,
Sommergruber
W,
Schweifer
N,
Wernitznig A, Beug H, Foisner R, Eger A
(2007) The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of
epithelial
polarity.
Oncogene
26
(49):6979–6988. https://doi.org/10.1038/
sj.onc.1210508
46. Spaderna S, Schmalhofer O, Wahlbuhl M,
Dimmler A, Bauer K, Sultan A, Hlubek F,
Jung A, Strand D, Eger A, Kirchner T,
Behrens J, Brabletz T (2008) The transcriptional repressor ZEB1 promotes metastasis
and loss of cell polarity in cancer. Cancer Res
68(2):537–544. https://doi.org/10.1158/
0008-5472.CAN-07-5682
47. Vandewalle C, Comijn J, De Craene B,
Vermassen P, Bruyneel E, Andersen H,
Tulchinsky E, Van Roy F, Berx G (2005)
SIP1/ZEB2 induces EMT by repressing
genes of different epithelial cell-cell junctions.
Nucleic Acids Res 33(20):6566–6578.
https://doi.org/10.1093/nar/gki965
48. Whiteman EL, Liu CJ, Fearon ER, Margolis B
(2008) The transcription factor snail represses
Crumbs3 expression and disrupts apico-basal
polarity
complexes.
Oncogene
27
(27):3875–3879. https://doi.org/10.1038/
onc.2008.9
49. De Craene B, Gilbert B, Stove C, Bruyneel E,
van Roy F, Berx G (2005) The transcription
factor snail induces tumor cell invasion
through modulation of the epithelial cell differentiation program. Cancer Res 65
(14):6237–6244. https://doi.org/10.1158/
0008-5472.CAN-04-3545
50. Ohkubo T, Ozawa M (2004) The transcription factor snail downregulates the tight junction
components
independently
of
E-cadherin downregulation. J Cell Sci 117
(Pt 9):1675–1685. https://doi.org/10.
1242/jcs.01004
51. Ikenouchi J, Matsuda M, Furuse M, Tsukita S
(2003) Regulation of tight junctions during
the epithelium-mesenchyme transition: direct
repression of the gene expression of claudins/
occludin by snail. J Cell Sci 116
(Pt 10):1959–1967. https://doi.org/10.
1242/jcs.00389
52. Martinez-Estrada OM, Culleres A, Soriano
FX, Peinado H, Bolos V, Martinez FO,
Reina M, Cano A, Fabre M, Vilaro S (2006)
The transcription factors slug and snail act as
repressors of Claudin-1 expression in epithelial cells. Biochem J 394(Pt 2):449–457.
https://doi.org/10.1042/BJ20050591
53. Peinado H, Olmeda D, Cano A (2007) Snail,
Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7(6):415–428. https://
doi.org/10.1038/nrc2131
54. Shamir ER, Pappalardo E, Jorgens DM,
Coutinho K, Tsai WT, Aziz K, Auer M, Tran
58
John-Poul Ng-Blichfeldt and Katja Ro ¨ per
Itzykson RA, Come C, Savagner P,
Gitelman I, Richardson A, Weinberg RA
(2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939. https://doi.org/
10.1016/j.cell.2004.06.006
39. Skrypek N, Goossens S, De Smedt E,
Vandamme N, Berx G (2017) Epithelial-tomesenchymal transition: epigenetic reprogramming driving cellular plasticity. Trends
Genet 33(12):943–959. https://doi.org/10.
1016/j.tig.2017.08.004
40. Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG, Evers BM, Zhou BP (2012) G9a
interacts with snail and is critical for snailmediated E-cadherin repression in human
breast cancer. J Clin Invest 122
(4):1469–1486. https://doi.org/10.1172/
JCI57349
41. Lin T, Ponn A, Hu X, Law BK, Lu J (2010)
Requirement of the histone demethylase
LSD1 in Snai1-mediated transcriptional
repression during epithelial-mesenchymal
transition. Oncogene 29(35):4896–4904.
https://doi.org/10.1038/onc.2010.234
42. Peinado H, Ballestar E, Esteller M, Cano A
(2004) Snail mediates E-cadherin repression
by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol
Cell Biol 24(1):306–319. https://doi.org/
10.1128/mcb.24.1.306-319.2004
43. Herranz N, Pasini D, Diaz VM, Franci C,
Gutierrez A, Dave N, Escriva M,
Hernandez-Munoz I, Di Croce L, Helin K,
Garcia de Herreros A, Peiro S (2008) Polycomb complex 2 is required for E-cadherin
repression by the Snail1 transcription factor.
Mol Cell Biol 28(15):4772–4781. https://
doi.org/10.1128/MCB.00323-08
44. Tong ZT, Cai MY, Wang XG, Kong LL, Mai
SJ, Liu YH, Zhang HB, Liao YJ, Zheng F,
Zhu W, Liu TH, Bian XW, Guan XY, Lin
MC, Zeng MS, Zeng YX, Kung HF, Xie D
(2012) EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a
co-repressor complex with HDAC1/
HDAC2 and snail to inhibit E-cadherin.
Oncogene 31(5):583–594. https://doi.org/
10.1038/onc.2011.254
45. Aigner K, Dampier B, Descovich L,
Mikula M, Sultan A, Schreiber M,
Mikulits W, Brabletz T, Strand D, Obrist P,
Sommergruber
W,
Schweifer
N,
Wernitznig A, Beug H, Foisner R, Eger A
(2007) The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of
epithelial
polarity.
Oncogene
26
(49):6979–6988. https://doi.org/10.1038/
sj.onc.1210508
46. Spaderna S, Schmalhofer O, Wahlbuhl M,
Dimmler A, Bauer K, Sultan A, Hlubek F,
Jung A, Strand D, Eger A, Kirchner T,
Behrens J, Brabletz T (2008) The transcriptional repressor ZEB1 promotes metastasis
and loss of cell polarity in cancer. Cancer Res
68(2):537–544. https://doi.org/10.1158/
0008-5472.CAN-07-5682
47. Vandewalle C, Comijn J, De Craene B,
Vermassen P, Bruyneel E, Andersen H,
Tulchinsky E, Van Roy F, Berx G (2005)
SIP1/ZEB2 induces EMT by repressing
genes of different epithelial cell-cell junctions.
Nucleic Acids Res 33(20):6566–6578.
https://doi.org/10.1093/nar/gki965
48. Whiteman EL, Liu CJ, Fearon ER, Margolis B
(2008) The transcription factor snail represses
Crumbs3 expression and disrupts apico-basal
polarity
complexes.
Oncogene
27
(27):3875–3879. https://doi.org/10.1038/
onc.2008.9
49. De Craene B, Gilbert B, Stove C, Bruyneel E,
van Roy F, Berx G (2005) The transcription
factor snail induces tumor cell invasion
through modulation of the epithelial cell differentiation program. Cancer Res 65
(14):6237–6244. https://doi.org/10.1158/
0008-5472.CAN-04-3545
50. Ohkubo T, Ozawa M (2004) The transcription factor snail downregulates the tight junction
components
independently
of
E-cadherin downregulation. J Cell Sci 117
(Pt 9):1675–1685. https://doi.org/10.
1242/jcs.01004
51. Ikenouchi J, Matsuda M, Furuse M, Tsukita S
(2003) Regulation of tight junctions during
the epithelium-mesenchyme transition: direct
repression of the gene expression of claudins/
occludin by snail. J Cell Sci 116
(Pt 10):1959–1967. https://doi.org/10.
1242/jcs.00389
52. Martinez-Estrada OM, Culleres A, Soriano
FX, Peinado H, Bolos V, Martinez FO,
Reina M, Cano A, Fabre M, Vilaro S (2006)
The transcription factors slug and snail act as
repressors of Claudin-1 expression in epithelial cells. Biochem J 394(Pt 2):449–457.
https://doi.org/10.1042/BJ20050591
53. Peinado H, Olmeda D, Cano A (2007) Snail,
Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7(6):415–428. https://
doi.org/10.1038/nrc2131
54. Shamir ER, Pappalardo E, Jorgens DM,
Coutinho K, Tsai WT, Aziz K, Auer M, Tran
58
John-Poul Ng-Blichfeldt and Katja Ro ¨ per